Maxgistine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MАXGISTIN (MAXGISTIN)

Composition:

Active substance: betahistine dihydrochloride;

1 tablet contains 8 mg, 16 mg, or 24 mg of betahistine dihydrochloride;

Excipients: microcrystalline cellulose, mannitol (E 421), citric acid monohydrate, colloidal anhydrous silicon dioxide, talc.

Pharmaceutical form. Tablets.

Main physicochemical properties:

8 mg tablets: white or almost white, round-shaped tablets, without a score line;

16 mg tablets: white or almost white, round-shaped tablets, with a score line;

24 mg tablets: white or almost white, round-shaped tablets, without a score line.

Pharmacotherapeutic group.

Agents for the treatment of vestibular disorders. ATC code N07CA01.

Pharmacological Properties

Pharmacodynamics

The mechanism of action of betahistine is only partially understood. There are several well-supported hypotheses regarding its mechanism of action.

Effect of betahistine on the histaminergic system:

Betahistine has been shown to exhibit partial agonist activity at H1 receptors and antagonist activity at H3 receptors of histamine in nervous tissue, with negligible activity at H2 histamine receptors. Betahistine increases histamine turnover and release by blocking presynaptic H3 receptors and inducing down-regulation of H3 receptors.

Betahistine may increase blood flow to the cochlear region and to the entire brain:

Betahistine improves circulation in the vessels of the stria vascularis of the inner ear, likely due to relaxation of precapillary sphincters in the microcirculatory system of the inner ear. Betahistine has also demonstrated an increase in cerebral blood flow in humans.

Betahistine promotes vestibular compensation:

Betahistine accelerates recovery of vestibular function following unilateral neurectomy in animals by stimulating and supporting the process of central vestibular compensation. This effect is characterized by enhanced regulation of histamine turnover and release and is mediated via H3 receptor antagonism. In humans, treatment with betahistine also reduced the recovery time of vestibular function after neurectomy.

Betahistine alters neuronal activity in vestibular nuclei:

Betahistine exerts a dose-dependent inhibitory effect on spike potential generation in neurons of the medial and lateral vestibular nuclei.

The pharmacodynamic properties of betahistine may provide a positive therapeutic effect of the drug on the vestibular system.

The efficacy of betahistine has been demonstrated in clinical studies in patients with vestibular vertigo and Ménière’s disease, shown by reduction in severity and frequency of vertigo attacks.

Pharmacokinetics

Absorption

After oral administration, betahistine is rapidly and almost completely absorbed throughout the gastrointestinal tract. Following absorption, the drug is quickly and almost entirely metabolized to the metabolite 2-pyridylacetic acid. Plasma concentrations of unchanged betahistine are very low. Therefore, all pharmacokinetic analyses are performed by measuring the concentration of the metabolite 2-pyridylacetic acid in plasma and urine.

When administered with food, the maximum concentration of the drug is lower compared to administration on an empty stomach. However, the total absorption of betahistine is identical in both cases, indicating that food intake only delays the absorption process.

Distribution

The percentage of betahistine bound to plasma proteins is less than 5%.

Biotransformation

After absorption, betahistine is rapidly and almost completely metabolized to 2-pyridylacetic acid (which has no pharmacological activity).

After oral administration of betahistine, plasma (and urinary) concentrations of 2-pyridylacetic acid reach peak levels within 1 hour and decline with a half-life of approximately 3.5 hours.

Elimination

2-Pyridylacetic acid is rapidly excreted in urine. After administration of betahistine at doses of 8–48 mg, approximately 85% of the initial dose is recovered in urine. Renal or fecal excretion of unchanged betahistine is negligible.

Linearity

Elimination rate remains constant following oral doses of 8–48 mg, indicating linear pharmacokinetics of betahistine and suggesting that the metabolic pathway involved is not saturable.

Clinical characteristics.

Indications.

Meniere's disease and Meniere's syndrome, characterized by three main symptoms:

• vertigo, sometimes accompanied by nausea and vomiting;
• hearing loss (deafness);
• tinnitus.

Symptomatic treatment of vestibular vertigo of various origins.

Contraindications.

Hypersensitivity to any component of the drug.

Pheochromocytoma.

Interaction with other medicinal products and other forms of interaction.

No in vivo studies have been conducted to investigate interactions with other medicinal products. Based on in vitro study data, inhibition of cytochrome P450 enzyme activity in vivo is not expected.

In vitro data indicate that metabolism of betahistine is inhibited by drugs which inhibit monoamine oxidase (MAO) activity, including MAO subtype B (e.g. selegiline). Caution is recommended when administering betahistine concomitantly with MAO inhibitors (including those selectively inhibiting MAO subtype B).

Since betahistine is a histamine analogue, interaction between betahistine and antihistamines may theoretically affect the efficacy of one or both agents.

Special precautions for use

During treatment with the drug, patients with bronchial asthma and/or a history of peptic ulcer of the stomach and duodenum should be carefully monitored.

Use during pregnancy or breastfeeding.

Pregnancy. There are no adequate data on the use of betahistine in pregnant women; therefore, the drug should not be prescribed during pregnancy except when clearly necessary.

Breastfeeding period. It is not known whether betahistine passes into human breast milk. The benefit of the drug to the mother should be weighed against the advantages of breastfeeding and the potential risk to the infant.

Ability to influence the reaction rate while driving or operating machinery.

Betahistine is indicated for the treatment of Ménière's syndrome, characterized by the classic triad of symptoms: vertigo, hearing loss, and tinnitus, as well as for symptomatic treatment of vestibular vertigo. Both conditions may negatively affect the ability to drive a vehicle or operate machinery. According to clinical studies evaluating the effect on the ability to drive and operate machinery, betahistine had no effect or only a negligible effect on this ability.

Dosage and Administration.

The daily dose for adults is 24–48 mg, evenly divided and administered throughout the day.

It is advisable to take tablets after meals. The dose should be individually adjusted according to the response. Improvement in symptoms may sometimes be observed only after 2–3 weeks of treatment. The best results are sometimes achieved with drug administration over several months. There is evidence that initiating treatment at an early stage of the disease prevents its progression and/or hearing loss at later stages.

Geriatric patients

Although data from clinical studies in this patient group are limited, extensive post-marketing experience suggests that dose adjustment in this population is not required.

Renal impairment

No specific studies have been conducted in this patient group; however, according to post-marketing experience, dose adjustment is not necessary.

Hepatic impairment

No specific studies have been conducted in this patient group; however, according to post-marketing experience, dose adjustment is not necessary.

Children.

As there is insufficient data on the safety and efficacy of betahistine in children, the drug is not recommended for use in this patient population.

Overdose.

There have been several reported cases of overdose. Mild to moderate symptoms (nausea, drowsiness, abdominal pain) were observed in some patients after ingestion of doses up to 640 mg. More severe complications (seizures, cardiopulmonary complications) occurred following intentional ingestion of high doses of betahistine, particularly in combination with overdose of other medicinal products.

Treatment: symptomatic and supportive therapy.

Side effects.

Gastrointestinal tract: nausea and dyspepsia, complaints of mild gastrointestinal disturbances (vomiting, gastrointestinal pain, abdominal distension and flatulence). These adverse effects usually resolve when the drug is taken with food or after dose reduction.

Nervous system: headache.

Immune system: hypersensitivity reactions, e.g. anaphylaxis.

Skin and subcutaneous tissue: skin and subcutaneous hypersensitivity reactions observed, including angioneurotic edema, rash, pruritus and urticaria.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 3 blisters per pack.

Prescription category. Prescription only.

Manufacturer. LLC "FARMEKS GROUP".

Manufacturer's address and place of business:

100 Shevchenka St., Boryspil, Kyiv region, Ukraine, 08301.

Date of last review.

All cases of adverse reactions should be reported to the manufacturer:

LLC "Farmeks Group", Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenka St., bld. 100,

tel.: +38(044)391-19-19, fax: +38(044)391-19-18, or via the form on the website: http://www.pharmex.com.ua/kontakty/forma-137-o/